The overall objective of this project is to develop an atomic-level of understanding of reversible oxygenation in representative oxygen transport proteins. The studies concern the mechanism of action and the control of reactivity in these metalloproteins. This research has several ramifications. It relates to the bioinorganic chemistry of metal centers in proteins, to general principles of protein conformation and interaction, to diversity of evolutionary adaptation to a physiological need, and to influences of dynamic flexibility in protein function. Moreover, we entertain the hypothesis that the active-center structures of invertebrate oxygen carriers can serve as molecular blueprints in the design of synthetic oxygen carriers that might be used as artificial blood supplements. The proposed research will involve the methods of crystallography, computer modeling various spectroscopic techniques and chemical synthesis. The research program includes six specific aims: (1) a detailed diffraction analysis of the physiologically relevant oxy and deoxy states of myohemerythrin; (2) a crystallographic study of quaternary diversity and interactions that control activity in oligomeric hemerythrins; (3) an analysis by means of computer modeling and by crystallography of the cooperative interactions in lamprey hemoglobin; (4) crystallization and study of viable oxygen-binding domains from giant molluscan hemocyanins; (5) collaborative spectroscopic studies of the hemerythrin active-center structure, of secondary structure in hemocyanins, of monoclonal antibody complexes with myohemerythrin, and of dynamics in the myohemerythrin structure; and (6) the design and synthesis of oligopeptide analogues of hemerythrin.